The bare bones of tissue regeneration and immunity with new ARMI group leader, Mikaël Martino
Although European at heart (he is both Swiss and French), Mikaël Martino is happily calling Australia home as he heads a new research group at ARMI. Arriving just a few months ago in April, he has already settled in nicely and set a cracking pace, working alongside the other researchers of the Martino Group.
The research group’s focus is to combine knowledge from the fields of bioengineering, stem cells and immunology to further understand the role the immune system plays in tissue repair and regeneration. The ultimate goal of the group is to design new regenerative strategies for the repair of bone and tissue.
The image shows reconstitution of a rat skull by micro computed tomography (microCT). The mineralised part of the bone appears in white. Two circular bone defects on the calvaria were regenerated after two months by the local delivery of engineered human growth factors. Mikaël Martino
Martino’s career in research began during his PhD at the Ecole Polytechnique Fédérale de Lausanne (Switzerland) in 2011. He then received grants from the Swiss National Science Foundation to take up a postdoctoral position at the Immunology Frontier Research Centre at Osaka University, Japan.
Tissue regeneration and immunity
It was at Osaka, where he rose to the role of assistant professor, that he made important contributions to the competitive field of regenerative medicine, the latest of which was a research paper that featured in the renowned publication Nature Communications. The paper, entitled “Inhibition of IL-1R1/MyD88 signalling promotes mesenchymal stem cell-driven tissue regeneration,” discusses how the innate immune system modulates the regeneration process, focusing, in particular, on injury to bone tissue. To understand exactly what the research paper is about, it’s best to get it straight from the horse’s mouth. Here’s what Martino had to say. “The paper is a study on the immune response that usually follows tissue injury. The immune response is triggered to protect us against potential pathogens invading the damaged tissue. Yet, even in the absence of pathogens, an immune response is triggered by danger signals released from necrotic cells, stressed cells, extracellular matrix fragments, etc. Receptors such as Toll-like receptors (TLRs) and interleukin-1 receptor (IL-1R) recognise these danger signals and trigger inflammation.” Martino then goes on to say, “Initially, the goal of the study was to determine whether TLRs and IL-1R are involved in the bone regeneration process. We found that the cytokine IL-1 via IL-1R negatively regulates bone regeneration. Interestingly, this negative regulation seems to act mainly on the local stem cells within the bone tissue. Indeed, IL-1 signalling drastically inhibits the capacity of the stem cells to make new bone.” Essentially, the paper showed that the innate immune response following injury makes the bone regeneration process less effective.
Clinical applications and challenges
Based on these findings, there is the potential to develop clinical applications, particularly for stem cell-based therapies for bones and even other tissue types. Currently, therapies of this kind struggle to show efficiency in clinical studies. The inability to meet benchmarks (efficacy, safety, practicality, cost-effectiveness and regulatory issues) have prevented the widespread use of regenerative therapies. However, it is foreseeable that could change if cellular and molecular mechanisms that should be targeted to drive regeneration are known. This will allow scientists to understand and subsequently control the immune regulation of regeneration, thus making regenerative therapies more effective. If this becomes possible, we may see therapies to augment bone regeneration in large craniomaxillofacial defects, bone degeneration in patients with osteonecrosis, distal tibial fractures, and periodontal disease.
His experience so far
There are many among the ARMI family who arrive from distant shores and it’s easy to forget that their experiences can be so different to those who were born and raised here. Martino has already experienced his transition to Australian life. He reflects on this and his first impressions of ARMI. “Coming to Australia from Japan is kind of a reverse culture shock, because I feel the lifestyle here is somehow similar to Europe, but establishing my lab is a new exciting adventure. I really like the way ARMI is designed, the friendly atmosphere and the accessibility of all people working here. This combined with top-notch facilities and the EMBL Australia package will be a great advantage to successfully continue my research program.”
We welcome Mikaël Martino to ARMI, and wish him the best of luck, and look forward to following his team’s progress into how the immune system modulates tissue repair and regeneration.